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The amygdala is a nuclear complex composed of 13 nuclei and cortical areas and their subdivisions. Tract-tracing studies performed over the past 20 years demonstrate that each nucleus is uniquely connected with other brain areas. Consistent with anatomic heterogeneity, the functions of the amygdala vary from attention to memory to formation of emotional responses to sensory stimuli. Here, we briefly review the principles of amygdaloid neuronal wiring that underlie the computations necessary to perform such complex behavioural functions.
Alzheimer's disease (AD) is characterized by deposition of β-amyloid (Aβ) in areas of the brain. Aβ is a metabolic fragment of the β-amyloid precursor protein (βAPP). Genetic evidence has linked βAPP to AD, and there is increasing evidence that fragments from βAPP are neurotoxic. Aβ, the main research focus, has been shown to induce depolarizing ion channel activity. Involvement of other cleaved products from βAPP are less clear. We have investigated the 105 amino acid C-terminal peptide (CT105) (containing the full sequence Aβ), an alternative fragment linked with cellular toxicity. CT105 induced non-selective ionic currents in Xenopus oocytes (a model cell used in cell signalling studies) and was toxic to oocytes and mammalian cortical neurones. These results suggest possible involvement of CT105 in inducing the neural toxicity characteristic of AD.
Neurodegeneration is often accompanied by protein inclusions which may interfere with cell physiology. On the other hand, alteration in intracellular trafficking may precede impairment of neurotransmission and therefore trigger cell death. In view of this, it is hypothesized that changes in mitochondrial traffic may occur before neurodegeneration triggered by rotenone exposure and could favor this process. The effects of low concentrations of rotenone on the expression of dynein clhl, dynactin and syntaphilin, which are proteins related to mitochondria transport and anchoring, were evaluated in cell cultures of substantia nigra, locus coeruleus and hippocampus as well as in these same brain areas in Lewis aged rats. The results indicate that low concentrations of rotenone decrease dynein clhl protein levels in cell cultures and brain areas of aged rats. Dynactin is decreased after exposure to 0.1 and 0.3 nM of rotenone, and increased after exposure to 0.5 nM of rotenone in cell cultures. Aged rats present increased dynactin expression. Syntaphilin expression decreased in vitro and increased in vivo after rotenone exposure. These findings suggest that changes in protein expression related to mitochondrial retrograde transport and anchoring occur before neurodegeneration induced by rotenone exposure, which may be a primary factor to trigger neurodegenerative mechanisms.
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